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Biomedical subjects

S R Bornstein

Publications and source records attributed to S R Bornstein.

158 records · Page 9Linked to original sources
PubMed1991

Role of the vasoactive intestinal peptide in a neuroendocrine regulation of the adrenal cortex.

Using a method for isolation and perfusion of pig adrenal glands with preserved nerve supply, we measured the release of cortisol and aldosterone and of the vasoactive intestinal peptide (VIP) after electrical stimulation of the splanchnic nerves. Additionally, the effect of VIP (at final concentrations of 10(-10)-10(-7) M) in the perfusion medium on the release of cortisol and aldosterone was investigated. The amount of VIP contained within the adrenal was measured by chromatography, and the localization of VIP in the adrenal gland was investigated immunohistochemically. Stimulation of the splanchnic nerves provoked a significant release of VIP (2.7- to 17-fold) and of the corticosteroids cortisol (2.5- to 6.7-fold) and aldosterone (1.6- to 2.8-fold). VIP added to the perfusion medium stimulated secretion of both corticosteroids with a maximal effect at 10(-8) M. Cortisol release increased 20- to 58.5-fold over basal, aldosterone release increased 2.9- to 4.9-fold over basal. This VIP-stimulated release had the same range of magnitude as the release stimulated by adrenocorticotropic hormone in physiological concentrations (10(-10) M). The mean concentration of VIP-like immunoreactivity in the adrenal glands was 8.9 +/- 2.1 pmol/g wet weight. Immunohistochemical investigations showed immunoreactive cells within the adrenal medulla as well as VIP-ergic nerve fibers in the cortex of the adrenal gland. These data show that the adrenal cortex can be stimulated independent of the hypothalamus-pituitary-adrenal axis via a neuroadrenocortical axis. In this regulatory pathway, the VIP-ergic innervation of the adrenal cortex may be a potent stimulatory element.

Adrenal Cortex↗
PubMed1991

Ultrastructural evidence for cortico-chromaffin hybrid cells in rat adrenals?

The adrenals of perfusion fixed rats were investigated by electron microscopy. In 2 out of 12 animals studied, chromaffin cells were detected that contained organelles identical to adrenocortical mitochondria and smooth endoplasmic reticulum. The mitochondria were round-shaped with the vesicular cristae typical for steroid hormone producing cells. They were located within the cytoplasm of adrenomedullary cells neighbouring chromaffin vesicles, rough endoplasmic reticulum and the characteristic elongated mitochondria of chromaffin cells with laminar cristae. The mitochondria-like structures could be clearly differentiated from the extracellularly located synaptic endings. It can therefore be concluded that some rare cortico-chromaffin hybrid cells or chromaffin cells that present a mitochondrial-endoplasmic system of adrenocortical cells exist within the adrenal medulla. This surprising finding may offer an explanation for the long line of inconsistencies in clinico-pathological reports of adrenal morphology.

Adrenal Cortex↗
PubMed1991

Adrenaline stimulates cholesterol side-chain cleavage cytochrome P450 mRNA accumulation in bovine adrenocortical cells.

The effect of adrenaline on the accumulation of mRNA encoding cholesterol side-chain cleavage cytochrome P450 (P450scc) and cortisol secretion was studied in bovine adrenocortical cells in primary culture. Treatment of cultured cells with adrenaline resulted in a 2-fold increase in mRNA encoding P-450scc, as revealed by Northern blot analysis. Under these conditions the maximal stimulation with ACTH resulted in a 6-fold accumulation of mRNA encoding P450scc. The effect of adrenaline on the expression of P450scc was abolished by the beta-blocker propranolol, while propranolol had no effect on ACTH-induced P450scc mRNA accumulation. Adrenaline stimulated the secretion of cortisol in a dose-dependent manner with a median effective dose of 0.5 mumol/l. The adrenaline-stimulated cortisol secretion amounted to 42% of the effect of ACTH (0.1 nmol/l). Upon adrenaline treatment, cAMP concentration in the culture medium increased about 50-fold over the basal value. It is concluded that the stimulatory action of adrenaline upon cortisol formation requires beta-adrenergic receptors and is due, at least in part, to a cAMP-mediated increases in the accumulation of mRNA encoding P450scc.

Adrenal Cortex↗
PubMed1990

Adrenocortical atrophy of hypophysectomized rats can be reduced by corticotropin-releasing hormone (CRH).

The effects of high dose injections of corticotropin-releasing hormone (CRH) on the adrenal cortex of hypophysectomized rats were studied at the light- and electron-microscopical levels. Adrenocortical atrophy induced by hypophysectomy could be reduced by daily i.p. injection of 10 micrograms (3 nmol) CRH given for 3 days starting at day 5 after the operation. The cortex broadened, mostly because of hypertrophy of the zona fasciculata. Blood vessels were enlarged. Although the adrenocortical cells of hypophysectomized rats showed features of a functionally suppressed state, such as tubular mitochondria, the cells of CRH-treated animals showed characteristics of stimulated cells. The inner membrane of the mitochondria formed the typical densely packed vesicles of adrenocortical cells that are active in steroidogenesis. Lipid droplets were found to be reduced, and the cells developed filopodia at their surface. These morphological observations indicate that CRH influences the adrenal cortex via extrapituitary mechanisms.

Adrenal Cortex↗
PubMed1990

Effects of splanchnic nerve stimulation on the adrenal cortex may be mediated by chromaffin cells in a paracrine manner.

The effects of nerve activation and of the catecholamines epinephrine and norepinephrine on adrenal corticosteroid release were investigated in intact isolated perfused pig adrenals with preserved nerve supply. To study the contact zones of medullary and cortical tissues, porcine adrenals were examined on the histological and ultrastructural levels. Splanchnic nerve activation stimulated in parallel the release of epinephrine (from a basal value of 0.31 +/- 0.11 to 8.13 +/- 0.60 microgram/min) and norepinephrine (from 0.76 +/- 0.68 to 12.94 +/- 3.58 micrograms/min) and the release of the corticosteroids cortisol (from 0.62 +/- 0.19 to 2.00 +/- 0.35 micrograms/min) and aldosterone (from 3.34 +/- 0.59 to 7.53 +/- 1.63 ng sigma in). Also, perfusion of the isolated adrenals with catecholamines provoked a significant release of the corticosteroids. Epinephrine (10(-6) M) stimulated the release of cortisol (from 0.59 +/- 0.31 to 2.66 +/- 0.34 micrograms/min) and aldosterone (from 2.12 +/- 0.42 to 4.68 +/- 0.92 ng/min). Norepinephrine (10(-6) M) stimulated the release of cortisol (from 0.26 +/- 0.07 to 1.28 +/- 0.10 micrograms/min) and aldosterone (from 1.28 +/- 0.37 to 3.57 +/- 0.80 ng/min). Using an immunostaining for synaptophysin, which is specific for neuroendocrine cells, chromaffin cells could be detected within all three zones of the adrenal cortex. The two endocrine tissues appear to be closely interwoven. On the ultrastructural level, medullary cells are in apposition to cortical cells, with close cellular contacts. These results show that the release of corticosteroids cortisol and aldosterone can be stimulated through the sympatho-adrenal system. Taking into consideration the close colocalization of cortical and medullary tissues, this stimulation may be mediated by chromaffin cells in a paracrine manner.

Adrenal Cortex↗
PubMedDate not supplied

Regulation of adrenocortical function by cytokines--relevance for immune-endocrine interaction.

The importance of the hypothalamic-pituitary-adrenalaxis (HPA) for the regulation of immunological functions has been greatly appreciated in the past (1-3). Activation of the HPA axis due to a given stimulus leads to a stress response which modulates the immune response. The interactions between the immune system and HPA-axis may be characterized by a circuit which includes I) activation of the HPA-axis and initiation of the stress response which, in term, has immune-modulating properties; II) a feedback mechanism derived from the immune system which regulates the HPA-axis. Current concepts on these regulatory circuits mainly favor the action of cytokines as mediators of the immune-endocrine regulation circuits which have been shown to interfere with the endocrine system on all levels of the HPA-axis. Over the past few years, it has become evident that the adrenal gland, itself, as the main effector organ of the HPA-axis, is a major site for both synthesis and action of numerous cytokines. This review summarizes current knowledge on production, action, as well as functional implications of cytokine action within the adrenal gland during development, health and disease.

Adrenal Cortex↗
PubMedDate not supplied

A new view on immune-adrenal interactions: role for Fas and Fas ligand?

The hypothalamic-pituitary-adrenal axis and the immune system interact in a bidirectional manner providing the basis for the regulation of the immune response due to a pathogenic stimulus. This interplay is commonly believed to be based on the action of hormones or cytokines, respectively. Since it has been detected that adrenocortical cells offer immunological properties such as expression of MHC class II antigens and/or CD95 (Fas antigen) and its ligand, the question has to be raised whether direct intercellular communication between immune cells and 'immunocompetent' endocrine cells contributes to the complexity of immunoregulation. Here we discuss the possible reciprocal relevance of physiological and pathological adrenal changes, as well as T-cell-mediated immune response for immune and/or adrenal pathology during disease.

Animals↗
PubMedDate not supplied

Sympathoadrenal regulation of adrenocortical steroidogenesis.

Sympathoadrenal regulation of adrenocortical steroidogenesis was studied on a physiological, cellular, molecular and morphological level. The effects of nerve activation and of epinephrine (EPI) on adrenal corticosteroid release were compared in isolated perfused pig adrenals with preserved nerve supply. Splanchnic nerve activation as well as perfusion with EPI provoked a significant release of cortisol, aldosterone and androstenedione. In cultured bovine adrenocortical cells steroid secretion and accumulation of P450scc, P450(17) alpha, P450c21 and P450(11) beta mRNAs were studied after stimulation with EPI with or without propranolol or phentolamine. Incubation with EPI stimulated steroidogenesis and increased the levels of all four P450-mRNAs. The beta-adrenergic antagonist propranolol totally blocked the effects of EPI while the alpha-antagonist phentolamine had no effect. Using immunohistochemistry, adrenals were studied morphologically. The contact zones of the two cell types were investigated on an electron microscopical level. Cortical and medullary cells were closely interwoven with cortical and chromaffin cells in direct apposition, providing the possibility for paracrine interactions. It is concluded that the release of corticosteroids can be stimulated through the sympatho-adrenal system. The stimulatory action of EPI upon adrenal steroid formation and accumulation of all four P450-mRNAs requires beta-adrenergic receptors. Taking into consideration the close colocalization of cortical and medullary tissue, this stimulation may be mediated by chromaffin cells in a paracrine manner.

Adrenal Cortex↗
PubMedDate not supplied

Leptin down-regulates the steroid producing system in the adrenal.

OB protein leptin inhibits the secretion of cortisol in primary cultures of bovine adrenocortical cells and down-regulates 17alpha-hydroxylase cytochrome P450 mRNA expression. To analyze if leptin regulates other major enzymes involved in adrenal steroidogenesis we tested its effect on mRNA expression for two further key enzymes, C21-hydroxylase (P450C21) and side-chain cleavage enzyme (P450SCC). Cultured bovine cortical cells were stimulated for 24 hours with 10 nM ACTH, with 10 nM ACTH plus 100 ng/ml leptin or left unstimulated as controls. Stimulation with ACTH led to a 1.75-fold increase of P450C21 mRNA and a 3.31-fold increase of P450SCC mRNA compared to unstimulated controls. Addition of leptin led to a reduction of ACTH-stimulated mRNA accumulation of 73% for P450C21 and of 45% for P450SCC. We therefore suggest that leptin reduces cortisol synthesis in the adrenal by down-regulating the steroid producing enzyme cascade in the cortical cell.

Adrenal Cortex Hormones↗
PubMedDate not supplied

The mercy of adrenocortical tumor cells on lymphocytes.

Immunologic escape includes the loss of Fas-receptor and the gain of Fas-ligand expression. Normal adrenal glands express the Fas-receptor and MHC class II molecules in inner cortical zones. A distinctive feature of adrenocortical tumors is the loss of MHC class II expression. Here we demonstrate loss of Fas and gain of Fas-ligand expression in the adrenocortical carcinoma cell line NCI-H295 by immunohistochemistry and RT-PCR. In a co-culture system of tumor cells and HLA-matched leukocytes, CD 8-positive or CD 4-positive lymphocytes, we examined the immunologic escape and the ability to induce apoptosis in the immune cells. The direct co-culture with either leukocytes, CD 8-positive or CD 4-positive lymphocytes reduced spontaneous apoptosis in immune cells from 49.9% to 13.0%, 8.6% and 15.3%, respectively, as determined by FACS analysis of Annexin V binding and LDH release in the medium. In co-culture, cortisol secretion increased up to 200%. Cellular communication does not induce apoptosis in immune cells, but promotes their survival. This may be due to partial HLA class I mismatches contributing to immunologic activity. The viability of the tumor cells was not affected, and these cells were stimulated to secrete cortisol. In summary, immune escape of adrenocortical carcinomas may occur because of altered Fas/Fas-L system expression and loss of MHC class H expression.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Basal catecholamine and cortisol secretion in primary chromaffin cell cultures before and after purification and retroviral transfection.

We have investigated the effects of supraphysiological concentrations of catecholamines on glucocorticoid secretion in vitro. These effects were analyzed in adrenocortical cells shown to be present in chromaffin cell cultures as well as in cortical cells cocultured with transfected chromaffin cells that overproduce catecholamines. Cortisol release from residual cortical cells in chromaffin cell cultures was found to be 2.5 times higher than from isolated adrenocortical cells. Removal of the adrenocortical cells from the chromaffin cells resulted in an almost complete cessation of cortisol secretion. Catecholamine overproduction was achieved by transfecting chromaffin cells with the blank retroviral vector pSAM-EN. Coculture of adrenocortical cells with these transfected chromaffin cells further enhanced the stimulating effect of chromaffin cells on cortisol 2.3-fold compared to normal cocultures. In conclusion, cortical cells in chromaffin cell cultures secrete significant amounts of cortisol, which should be considered when evaluating the endocrine function of these cell cultures and which can be abolished by purification. The hormonal activity of adrenocortical cells is highly increased in an environment of catecholamine overproduction, which is of both basic and clinical importance.

Adrenal Cortex↗
PubMedDate not supplied

Differential expression of prolactin receptor (PRLR) in normal and tumorous adrenal tissues: separation of cellular endocrine compartments by laser capture microdissection (LCM).

PRL stimulates adrenal steroidogenesis. In this study, we compared the PRLR expression in normal and tumorous adrenal tissues and investigated a potential proliferative effect of PRL in adrenal cells. mRNA expression of long and intermediate forms of PRLR was detected in both normal adrenal cortex as well as benign and malignant adrenal tumors and in the human adrenocortical carcinoma cell line NCI-H295. Molecular analysis of cells procured by LCM clearly demonstrated that PRLR mRNA is expressed in the adrenal cortex but not in the medulla. Immunostaining revealed PRLR protein in all three zones of the normal adrenal cortex. Furthermore, adrenal carcinomas and adenomas stained positive for the PRLR, while in phaeochromocytomas as in the normal adrenal medulla, no specific staining was observed. By WST-1 test, we could show that PRL (10(-7) M) decreased proliferation and viability of adrenal cells in primary cell culture suggesting that PRL is not a mitogenic factor of adrenocortical cells.

Adrenal Cortex↗
PubMedDate not supplied

Morphological changes in adrenals from victims of suicide in relation to altered apoptosis.

Endocrine dysfunction may cause psychiatric symptoms and, vice versa, psychiatric diseases may lead to endocrine alterations. The adrenal as the end organ of both the hypothalamic-pituitary-adrenocortical and sympatho-adrenal axes is subject to the functional changes of the stress system. Thus, increased adrenal gland weight was observed previously in victims of violent suicide. This study was designed to analyze the morphological and morphodynamic changes of adrenals from suicide victims. We investigated 30 adrenals obtained from 15 suicide victims using immunohistochemistry and a computerized video system. In addition, apoptosis and cell proliferation were analyzed. We found a significant enlargement of the adrenal cortex to 158.8% (SD = 29.8%, p < 0.01) that was restricted to the two inner zones only (zona reticularis, 161.6 +/- 35.3%; zona fasciculata, 186.4 +/- 34.4%). This increase in adrenocortical size correlated with a decrease in the number of apoptotic cells within the zona fasciculata. In conclusion, these results clearly demonstrate chronic structural adrenal changes in suicide victims. The adrenal gland mirrors the functional changes of the stress system which leaves an imprint on the morphology of the gland.

Adrenal Glands↗